Fig 6

Targeting MSLN and MET therapeutically inhibits lung cancer BM in vivo. PC9-BrM cells and PC9-BrM cells with MSLN knockdown (shMSLN) were injected into nude mice via the left ventricle. Nude mice injected with PC9-BrM cells were randomly assigned to the following administration regimen groups and continued to be administered for 5 weeks from the day 3 post-injection: Control, placebo administration; anetumab, anetumab (0.2 mg/kg) intravenously weekly; crizotinib, crizotinib (5 mg/kg) intraperitoneally every 2 days; anetumab+crizotinib, anetumab (0.2 mg/kg) intravenously weekly and crizotinib (5 mg/kg) intraperitoneally every 2 days; capmatinib, oral capmatinib (10mg/kg) daily; anetumab+capmatinib, anetumab (0.2 mg/kg) intravenously weekly and oral capmatinib (10mg/kg) daily. A Fluorescent images showing BBB permeability of the mouse brains after intravenous injection of Texas Red-Dextran (70,000 MW), DyLight 488-Lycopersicon Esculentum Lectin (LEL) (n=3 in each group). Cell nuclei are stained with DAPI (blue). Scale bar, 75 μm. B Representative biofluorescence images of each group at the indicated time. C Results for distant metastasis in each group. D Survival curves for the different groups (n=8 in each group). E Representative biofluorescence images of each group at the indicated times. F Results for distant metastasis in each group. G Survival curves for the different groups (n=5 in each group). H Schematic description of the role of MSLN in promoting lung cancer BM by disrupting the BBB. (Data are presented as mean ± SD)